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Perfluorooctylbromide coated block polymer ultrasound microbubble contrast agent and preparation method thereof

A block polymer, ultrasonic microbubble technology, applied in echo/ultrasonic imaging agents, etc., can solve the problems of poor contrast effect, hard shell, reduced signal-to-noise ratio, etc., to achieve enhancement effect, good flexibility, and excellent stability. Effect

Inactive Publication Date: 2013-12-11
FUJIAN MEDICAL UNIV UNION HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, some polymer materials, such as polylactic-glycolic acid, make the contrast agent shell hard, and it is difficult to develop the second harmonic imaging contrast-enhanced ultrasound with a low mechanical index. High acoustic output is required to cause nonlinear vibration or rupture of microbubbles. Enhanced contrast imaging is produced, but at the same time the background tissue echo signal is also significantly enhanced, resulting in a significant decrease in the signal-to-noise ratio and poor contrast effects

Method used

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  • Perfluorooctylbromide coated block polymer ultrasound microbubble contrast agent and preparation method thereof
  • Perfluorooctylbromide coated block polymer ultrasound microbubble contrast agent and preparation method thereof
  • Perfluorooctylbromide coated block polymer ultrasound microbubble contrast agent and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0028] 1. Preparation of contrast agent

[0029]Weigh 0.2g mPEG-PLLA (molecular weight 5000 / 5000, product of Jinan Daigang Bioengineering Co., Ltd.) dissolved in 2ml tetrahydrofuran, put it into a dialysis bag, dialyze against normal saline overnight, change the dialysate twice during the period; take 1ml 1 wt % mPEG-PLLA normal saline solution, ice bath pre-cooling, add 40μl perfluoropentane, under ice bath conditions, 35000rpm electric homogenization for 2min, get block polymer ultrasonic microbubble contrast agent wrapped in perfluoropentane , in the form of a milky white suspension. The aforementioned mPEG is monomethoxypolyethylene glycol, and PLLA is L-polylactic acid.

[0030] 2. Characterization of contrast agent

[0031] After diluting the microbubble contrast agent with normal saline, observe it under an inverted microscope. The microbubbles are round, well dispersed, smooth and translucent, and relatively uniform in size (see figure 1 ), the average particle size...

Embodiment 2

[0041] Preparation of mPEG-PLLA contrast agent by phacoemulsification method different from that in Example 1

[0042] Weigh 0.2g mPEG-PLLA (molecular weight 5000 / 5000, product of Jinan Daigang Bioengineering Co., Ltd.) dissolved in 2ml tetrahydrofuran, put it into a dialysis bag, dialyze against normal saline overnight, change the dialysate twice during the period; take 1ml 1 wt % mPEG-PLLA normal saline solution, ice bath pre-cooling, add 40 μl liquid perfluoropentane, under ice bath conditions, 200W ultrasonic emulsification for 1min, the result is a mixture of large particle size microbubbles and microcapsules wrapped with saline, The particle size of the microbubble is about 6-50 μm, and the particle size of the microcapsule is about 3-7 μm.

Embodiment 3

[0044] Preparation of Block Polymer mPEG-PCL Contrast Agent

[0045] Weigh 0.2g mPEG-PCL (molecular weight 5000 / 5000, product of Jinan Daigang Bioengineering Co., Ltd., PCL is polycaprolactone) dissolved in 2ml tetrahydrofuran, put it into a dialysis bag, dialyze against normal saline overnight, and change dialysis in between solution twice; take 1ml 1 wt% mPEG-PCL physiological saline solution, pre-cool in an ice bath, add 40μl liquid perfluoropentane, under ice bath conditions, 200W ultrasonic emulsification for 1min, to obtain polymer microbubble contrast agent, microbubble average The particle size is larger (4.5±1.2) μm, and the density is lower at 1.2×10 8 / ml.

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Abstract

The invention discloses a perfluorooctylbromide coated block polymer ultrasound microbubble contrast agent and a preparation method thereof. The perfluorooctylbromide coated block polymer ultrasound microbubble contrast agent refers to a perfluorooctylbromide coated mPEG-PLLA, PLGA-PEG-PLGA or mPEG-PCL block polymer ultrasound microbubble contrast agent. A preparation method of the agent comprises the steps of preparing an mPEG-PLLA, PLGA-PEG-PLGA or mPEG-PCL block polymer solution, adding perfluorooctylbromide perfluoropentane, perfluorohexane or perfluoropropane to the solution, and then preparing the ultrasound microbubble contrast agent by an electric internal cutting homogenizing, ultrasonic emulsifying or mechanical oscillating method. The perfluorooctylbromide coated block polymer ultrasound microbubble contrast agent provided by the invention is applied to preparation of an ultrasonic imaging diagnosis contrast agent. The high polymer material used by the perfluorooctylbromide coated block polymer ultrasound microbubble contrast agent is safe and nontoxic, and is obviously cheaper than synthetic phospholipids; the microbubble preparation process is simple and convenient; the novel perfluorooctylbromide coated block polymer ultrasound microbubble contrast agent has good potential prospect in clinical application.

Description

technical field [0001] The invention relates to an ultrasonic microbubble contrast agent in which a fluorocarbon compound capable of liquid-gas phase transition is wrapped by a block polymer, and belongs to the field of ultrasonic image diagnosis. Background technique [0002] Ultrasonic microbubble contrast agent has been widely used in the diagnosis of clinical diseases, which has significantly improved the coincidence rate of ultrasound diagnosis, and is a "milestone" in the history of ultrasound medical development. At present, most of the ultrasound contrast agents used clinically are inert gases wrapped in lipids or albumin, which have poor stability and are prone to spontaneous rupture. [0003] Polymer materials have the advantages of good biocompatibility and biodegradability. The use of polymer materials to prepare ultrasonic microbubble contrast agents has uniform particle size distribution, high stability, and good compression resistance. It has become a hot spot...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/22
Inventor 陈志奎林礼务薛恩生何以敉陈琬萍黄丹凤
Owner FUJIAN MEDICAL UNIV UNION HOSPITAL
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